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siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro

INTRODUCTION: AKR1C3, as a crucial androgenic enzyme, implicates the androgen biosynthesis and promoting prostate cancer cell growth in vitro. This study provides a new gene therapy strategy for targeting AKR1C3 to treat castration-resistant prostate cancer. METHODS: siAKR1C3@PPA is assembled from P...

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Autores principales: Cui, Xiaoli, Yao, Zhou, Zhao, Tianyu, Guo, Jiahui, Ding, Jipeng, Zhang, Siwei, Liang, Zuowen, Wei, Zhengren, Zoa, Alexis, Tian, Yuantong, Li, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800608/
https://www.ncbi.nlm.nih.gov/pubmed/36591491
http://dx.doi.org/10.3389/fonc.2022.1069033
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author Cui, Xiaoli
Yao, Zhou
Zhao, Tianyu
Guo, Jiahui
Ding, Jipeng
Zhang, Siwei
Liang, Zuowen
Wei, Zhengren
Zoa, Alexis
Tian, Yuantong
Li, Jing
author_facet Cui, Xiaoli
Yao, Zhou
Zhao, Tianyu
Guo, Jiahui
Ding, Jipeng
Zhang, Siwei
Liang, Zuowen
Wei, Zhengren
Zoa, Alexis
Tian, Yuantong
Li, Jing
author_sort Cui, Xiaoli
collection PubMed
description INTRODUCTION: AKR1C3, as a crucial androgenic enzyme, implicates the androgen biosynthesis and promoting prostate cancer cell growth in vitro. This study provides a new gene therapy strategy for targeting AKR1C3 to treat castration-resistant prostate cancer. METHODS: siAKR1C3@PPA is assembled from PEG3500, PAMAM, Aptamer-PSMA, and siRNA for AKR1C3. We analyzed the relationship between AKR1C3 expression and the survival rate of prostate cancer patients based on the GEPIA online database to perform disease-free survival, and found that AKR1C3 may be an important factor leading to poor prognosis in prostate cancer. Considering AKR1C3 as a therapeutic target for castration-resistant prostate cancer, we constructed a complex nucleic acid nanoparticle, siAKR1C3@PPA to investigate the inhibitory effect on castration-resistant prostate cancer. RESULTS: Aptamer-PSMA acts as a target to guide siAKR1C3@PPA into PSMA-positive prostate cancer cells and specifically down regulate AKR1C3. Cyclin D1 was decreased as a result of siAKR1C3@PPA treatment. Changes in Cyclin D1 were consistent with decreased expression of AKR1C3 in LNCaP-AKR1C3 cells and 22RV1 cells. Furthermore, in the LNCaP-AKR1C3 group, 1070 proteins were upregulated and 1015 proteins were downregulated compared to the LNCaP group according to quantitative 4D label-free proteomics. We found 42 proteins involved in cell cycle regulation. In a validated experiment, we demonstrated that PCNP and CINP were up-regulated, and TERF2 and TP53 were down-regulated by western blotting. CONCLUSION: We concluded that siAKR1C3@PPA may arrest the cell cycle and affect cell proliferation.
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spelling pubmed-98006082022-12-31 siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro Cui, Xiaoli Yao, Zhou Zhao, Tianyu Guo, Jiahui Ding, Jipeng Zhang, Siwei Liang, Zuowen Wei, Zhengren Zoa, Alexis Tian, Yuantong Li, Jing Front Oncol Oncology INTRODUCTION: AKR1C3, as a crucial androgenic enzyme, implicates the androgen biosynthesis and promoting prostate cancer cell growth in vitro. This study provides a new gene therapy strategy for targeting AKR1C3 to treat castration-resistant prostate cancer. METHODS: siAKR1C3@PPA is assembled from PEG3500, PAMAM, Aptamer-PSMA, and siRNA for AKR1C3. We analyzed the relationship between AKR1C3 expression and the survival rate of prostate cancer patients based on the GEPIA online database to perform disease-free survival, and found that AKR1C3 may be an important factor leading to poor prognosis in prostate cancer. Considering AKR1C3 as a therapeutic target for castration-resistant prostate cancer, we constructed a complex nucleic acid nanoparticle, siAKR1C3@PPA to investigate the inhibitory effect on castration-resistant prostate cancer. RESULTS: Aptamer-PSMA acts as a target to guide siAKR1C3@PPA into PSMA-positive prostate cancer cells and specifically down regulate AKR1C3. Cyclin D1 was decreased as a result of siAKR1C3@PPA treatment. Changes in Cyclin D1 were consistent with decreased expression of AKR1C3 in LNCaP-AKR1C3 cells and 22RV1 cells. Furthermore, in the LNCaP-AKR1C3 group, 1070 proteins were upregulated and 1015 proteins were downregulated compared to the LNCaP group according to quantitative 4D label-free proteomics. We found 42 proteins involved in cell cycle regulation. In a validated experiment, we demonstrated that PCNP and CINP were up-regulated, and TERF2 and TP53 were down-regulated by western blotting. CONCLUSION: We concluded that siAKR1C3@PPA may arrest the cell cycle and affect cell proliferation. Frontiers Media S.A. 2022-12-16 /pmc/articles/PMC9800608/ /pubmed/36591491 http://dx.doi.org/10.3389/fonc.2022.1069033 Text en Copyright © 2022 Cui, Yao, Zhao, Guo, Ding, Zhang, Liang, Wei, Zoa, Tian and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Cui, Xiaoli
Yao, Zhou
Zhao, Tianyu
Guo, Jiahui
Ding, Jipeng
Zhang, Siwei
Liang, Zuowen
Wei, Zhengren
Zoa, Alexis
Tian, Yuantong
Li, Jing
siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
title siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
title_full siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
title_fullStr siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
title_full_unstemmed siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
title_short siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
title_sort siakr1c3@ppa complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800608/
https://www.ncbi.nlm.nih.gov/pubmed/36591491
http://dx.doi.org/10.3389/fonc.2022.1069033
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